3-N-butylphthalide (NBP) attenuates the amyloid-β-induced inflammatory responses in cultured astrocytes via the nuclear factor-κB signaling pathway

Cell Physiol Biochem. 2013;32(1):235-42. doi: 10.1159/000350139. Epub 2013 Jul 26.

Abstract

Background/aims: Activation of astrocytes is a common feature of Alzheimer's disease (AD). Proinflammatory molecules produced by activated astrocytes contribute to neuronal damage in AD. Moreover, dl-3-n-butylphthalide (NBP) has been reported to attenuate astroglial activation and exert neuroprotective effects in AD transgenic mice. However, the mechanism by which NBP inhibits activated astrocytes is poorly understood.

Methods: In this study, the primary astrocytes were obtained from the cerebral cortices of 1-day-old Sprague-Dawley rats. The levels of GFAP, COX-2, NF-κB, and IκBα were examined by Western blotting and the levels of TNF-α and IL-6 were determined by ELISA.

Results: NBP inhibited the amyloid-β (Aβ)-induced activation of astrocytes and the up-regulation of proinflammatory molecules. Importantly, NBP markedly suppressed Aβ-induced IκBα degradation and nuclear factor-κB (NF-κB) translocation.

Conclusion: Our results suggest that NBP attenuates Aβ-induced activation of astrocytes and neuroinflammation via inhibition of the NF-κB signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / pharmacology*
  • Animals
  • Astrocytes / cytology
  • Astrocytes / drug effects*
  • Astrocytes / metabolism
  • Benzofurans / pharmacology*
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Cyclooxygenase 2 / metabolism
  • I-kappa B Proteins / metabolism
  • Interleukin-6 / metabolism
  • Mice
  • Mice, Transgenic
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / metabolism*
  • Nerve Tissue Proteins / metabolism
  • Neuroprotective Agents / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • Transcription Factor RelA / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation / drug effects

Substances

  • Amyloid beta-Peptides
  • Benzofurans
  • I-kappa B Proteins
  • Interleukin-6
  • NF-kappa B
  • Nerve Tissue Proteins
  • Neuroprotective Agents
  • Nfkbia protein, mouse
  • Nfkbia protein, rat
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha
  • NF-KappaB Inhibitor alpha
  • 3-n-butylphthalide
  • Cyclooxygenase 2